The gut microbiota (GM) has been linked to the development, progression, and response to therapy in plasma cell neoplasms (PCNs). The primary goal of this study was to investigate the relationship between the composition of the GM before and during autologous hematopoietic stem cell transplant (HSCT) with clinical outcomes of patients with PCNs. We focused on the genus Faecalibacterium, which includes the most abundant anaerobic commensal bacterium in the GM. Fecal samples were collected prospectively before, mid (at 1 week from the start of intervention), and end (at engraftment) of intervention (liberalized vs neutropenic diet) and subjected to 16S ribosomal DNA sequencing. Eighty-three patients were enrolled. Their median age was 64 (range, 31-79) years. Fifty-four patients received HSCT as part of frontline therapy and 29 for relapsed/refractory disease. With median follow-up time for survivors (n = 82) of 32 (range, 0.7-61) months, the median progression-free survival (PFS) was 40 months. Higher preintervention Faecalibacterium abundance was associated with improved PFS (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.86-0.99; P = .02). Faecalibacterium abundance was found to decrease early after transplant (P < .01). Although the administration of high-dose melphalan (200 mg/m2) was significantly associated with PFS in both univariable (HR, 0.38, 95% CI, 0.19-0.75; P = .006) and multivariable (HR, 0.42; 95% CI, 0.20-0.87; P = .02) analyses, preintervention Faecalibacterium abundance remained independently associated with PFS (HR, 0.93; 95% CI, 0.86-0.99; P = .04) on multivariable analysis. In conclusion, lower preintervention Faecalibacterium abundance was associated with inferior PFS.

INTRODUCTION Allogeneic hematopoietic cell transplantation (alloHCT) is indicated in patients (pts) with FLT3-ITD mutated AML. The randomized BMT CTN 1506 trial (Levis et al. JCO) demonstrated that maintenance with FLT3 inhibitor gilteritinib (gilt) significantly improved relapse-free survival (RFS) among pts with detectable peri-alloHCT minimal residual disease (MRD) but was also associated with a greater degree of myelosuppression and infections. In older pts, aged >60 years, increasing post-HCT toxicity may adversely impact outcomes. On this basis, we performed a post-hoc analysis of pts aged > 60 years enrolled onto BMT CTN 1506 to examine the impact of gilteritinib maintenance in older pts. METHODS Pts ≥60 years randomized on BMT CTN 1506 (gilt=47, placebo=57; N=104) were included. The primary endpoint of this post-hoc analysis was RFS. We additionally assessed overall survival (OS), incidence of relapse, non-relapse mortality (NRM) in all pts and in pts with detectable MRD. RESULTS Baseline characteristics were balanced. Age was similar (65.2 vs 64.7 years; p = 0.12), as was prior TKI exposure, and NPM1 mutation status. Myeloablative conditioning (MAC) was used in 8 (17%) pts randomized to gilt and 18 (32%) pts randomized to placebo (p=0.08). Median f/u of survivors was 43.8 months (range:1-61 mo.). Estimated RFS and OS at 48 months were not different between groups (RFS: gilt: 57.0%, 95%CI 44.1-73.7%, placebo: 57.1%, 95%CI 45.4-71.8%; OS: gilt: 56.9%, 95%CI 42.9-46.7%, placebo: 58.4%, 95%CI 46.7-73.1%). While gilt assignment did not affect survival, several predictors of poorer survival were identified including use of reduced intensity conditioning (RIC) (HR = 3.46; p = 0.014), use of calcineurin inhibitor/MTX for graft-vs-host disease (GVHD) prophylaxis (HR = 2.29; p = 0.041), high-risk cytogenetics (HR = 2.64; p = 0.021), and MRD (+) pre-HCT (HR = 2.29; p = 0.018). Finally, relative to gilt assignment, opposing rates of relapse and NRM were observed. The incidence of relapse was lower with gilt (16%, 95%CI 6.8-28% vs 32%, 95%CI 20-45%, p=0.046) but NRM was higher (27%, 95%CI 15-41% vs 11%, 95% CI 4.3-21%, p=0.033). We next analyzed the 49 pts (gilt=22, placebo=27) with detectable peri-HCT MRD. RFS and OS again were not different (RFS: gilt: 44.4%, 95%CI 27.1-72.7%, placebo: 43.8%, 95%CI 28.4-67.5%, OS: gilt: 49.2%,95%CI, 31.3-77.4%, placebo: 55.6%, 95%CI 39.4-77.8%). The incidence of relapse trended lower in gilt pts (25%, 95%CI, 5.3-44.7% vs 45% (95%CI, 25-63%), p=0.2) while NRM trended higher (31%, 95%CI 12-52% vs 11%, 95%CI, 2.7-26%, p=0.12). Seventeen (36%) patients completed planned 2 year maintenance with gilt compared to 29 (51%) completing therapy with placebo. Median time on gilt was 13.2 months. The most common reason for discontinuation was adverse events (n=19, 40%), of which cytopenias (n=8) and infections (n=4) were most frequent. Non-relapse causes of death among gilt treated pts included infections (n=8), intracranial hemorrhage related to thrombocytopenia (n=1), second cancer (n=1), and Guillain-Barre syndrome (n=1). Most infections (n=5) were attributed to GVHD as an underlying cause. CONCLUSION Among pts aged ≥60 years, gilt maintenance did not improve RFS or OS. Gilt use was associated with reduced relapse regardless of peri-HCT MRD status demonstrating disease effect; however, higher NRM limited overall benefit. In older FLT3 mutated pts, employing strategies to mitigate HCT related toxicity, e.g. alternative GVHD prophylaxis strategies, may better accommodate use of maintenance therapy including gilt. Lower doses of gilt (particularly with azole co-use) may be worth exploring to mitigate drug AEs, improve compliance, thus further improving benefit.

BMT CTN 1506 ("MORPHO"; NCT02997202) was a randomized phase 3 study of gilteritinib compared to placebo as maintenance therapy after hematopoietic stem cell transplantation (HCT) for patients with FLT3-ITD-mutated acute myeloid leukemia (AML). A key secondary endpoint was to determine the impact on survival of pre- and/or post-HCT measurable residual disease (MRD), as determined using a highly sensitive assay for FLT3-ITD mutations. Generally, gilteritinib maintenance therapy was associated with improved relapse-free survival (RFS) for participants with detectable peri-HCT MRD, whereas no benefit was evident for those lacking detectable MRD. We conducted a post-hoc analysis of the data and found that the level of MRD detected with this approach correlated remarkably with RFS and relapse risk, and that MRD detectable at any level negatively impacted RFS. In the placebo arm, 42.2% of participants with detectable FLT3-ITD MRD relapsed compared to 13.4% of those without detectable MRD. We found that 14.8% of participants had multiple FLT3-ITD clones detected as MRD and had worse survival irrespective of treatment arm. Finally, we examined the kinetics of FLT3-ITD clonal relapse or eradication and found that participants on the placebo arm with detectable MRD relapsed rapidly after HCT, often within a few weeks. MRD-positive participants on the gilteritinib arm relapsed either with FLT3 wild type clones (as assessed by capillary electrophoresis), after cessation of gilteritinib with persistent MRD, or on progression of multi-clonal disease. These data demonstrate the potential of using FLT3-ITD MRD to guide therapy with gilteritinib for this subtype of AML.

Introduction:To ensure response is preserved, it is common practice to continue chemotherapy in patients with large B-cell lymphoma (LBCL) awaiting autologous hematopoietic stem cell transplant (HSCT), even after they have achieved complete or partial response (CR/PR). Methods:We conducted a retrospective chart review of patients with LBCL evaluated at our institution between 2011 and 2022 to examine the effect of delay of transplant and continuation of chemotherapy past CR/PR on progression of disease (PD) prior to transplant. The association of PD prior to transplant with delayed transplant and additional chemotherapy was modeled using logistic regression. Results:Out of the 87 patients included, 74 (85%) had relapsed/refractory LBCL. Transplant was delayed in 20 (23%) patients, and 22 (25%) patients received chemotherapy after CR/PR. Delay of transplant was associated with higher odds of PD prior to transplant (odds ratio [OR] = 4.0, p = 0.034), as was additional chemotherapy use after CR/PR (OR = 2.2, p = 0.09). Conclusion:Proceeding to autologous HSCT as soon as adequate response is achieved in LBLC was associated with a lower likelihood of progression of disease prior to transplant regardless of additional chemotherapy receipt. Trial Registration:The authors have confirmed that clinical trial registration is not needed for this submission.

IntroductionSerum soluble B-cell maturation antigen (sBCMA) has been shown to correspond to high disease burden in uncontrolled Multiple Myeloma (MM). However, it has not been extensively evaluated as a biomarker of minimal/measurable residual disease (MRD). MethodsIn this prospective observational correlative study, the primary objective was to correlate serum sBCMA with tumor burden in the bone marrow (BM) of patients with MM evaluated for first or salvage autologous stem cell transplantation. Paired samples were collected from 44 patients. BM overt disease was identified on morphological analysis or by standard flow cytometry (limit of detection (LOD) of 10-1). BM MRD was assessed by MRD flow cytometry (sensitivity of 1 aberrant clonal plasma cell in 105 nucleated cells) and/or next-generation sequencing (LOD of 10-6). ResultsFor transplant recipients (n= 36), the mean serum sBCMA (standard deviation (SD)) was 18.1 (11.7) ng/mL, BM overt disease was present in 12 (33.3%) patients and MRD only/No MRD in 20 (55.6%) patients. For non-transplanted patients (n= 8), the mean serum sBCMA was 9.7 (5.2) ng/mL, BM overt disease was present in 1 (12.5%) patient, while MRD only/No MRD in 5 (62.5%) patients. Serum sBCMA was associated with overt disease (p < 0.001), as well as MRD only/No MRD (p= 0.002). On multivariable logistic regressions modeling, higher serum sBCMA indicated higher odds of BM overt disease (odds ratio (OR) = 1.12, p = 0.007) and lower odds of MRD only/No MRD (OR = 0.91, p = 0.03). ConclusionSerum sBCMA was associated not only with BM overt disease, but also with BM detectable or below LOD MRD.

Aims BMT CTN 1506 (“MORPHO”) was a global phase 3 study of post-hematopoietic cell transplantation (HCT) maintenance with gilteritinib versus placebo for patients with FLT3-ITD-mutated AML in CR1. The study did not meet its primary endpoint of improved relapse-free survival (RFS) for post-HCT gilteritinib, but subgroup analysis indicated a benefit for participants with pre-HCT measurable residual disease (MRD). Subgroup analysis also indicated a statistically significant benefit of post-HCT gilteritinib for participants in North America, but no benefit for those in Europe or Asia. RFS for the control arms in Europe and Asia was higher than anticipated, suggesting that participants with different disease biology may have accrued to the study in these different geographic regions. In the primary analysis of the study, pre-HCT FLT3 inhibitor use and MRD across the entire study population were both found to have impacted outcomes. Time from diagnosis to HCT, a reflection of local practice patterns, is also known to impact outcomes for FLT3-ITD AML. We hypothesized that local practice patterns of pre-HCT FLT3 inhibitor use and time from AML diagnosis to HCT could have influenced the disease biology of study pts at the time of enrollment. This would be predicted to result in pre-HCT MRD levels and could provide an explanation for the regional differences observed in the study outcome. Methods We conducted a post-hoc analysis of the data focusing on days from AML diagnosis to HCT, pre-HCT FLT3 inhibitor use, and FLT3-ITD MRD assessed by a high-sensitivity assay. Eligibility requirements included FLT3-ITD-mutated AML in first remission after intensive chemotherapy and HCT occurring within 12 months of achieving remission. Patients refractory to induction therapy, or those with a history of relapse, were ineligible. Results Accrual took place in 16 different countries, with 5 countries accounting for 79.7% of the total accrual: USA 42.7%; Japan 15.7%; Korea 8.4%; UK 6.7%; Germany 6.2%; other countries 20.2%. In two countries, USA and Germany (48.9% of total enrollment), participants underwent HCT a median of 119 days after AML diagnosis, and 90.2% were treated with a FLT3 inhibitor pre-HCT. In contrast, in Japan, Korea, the UK and the other 11 countries all combined, participants underwent HCT a median of 152.5 days after AML diagnosis, and only 30.8% received any FLT3 inhibitor pre-HCT. Amongst all participants, those transplanted < 120 days from AML diagnosis and/or those treated with FLT3 inhibition pre-HCT were more likely to have improved RFS from post-HCT gilteritinib. RFS was improved with post-HCT gilteritinib in the US and Germany (HR 0.397; CI 0.220-0.718), whereas no benefit was evident in all other countries combined (HR 1.184; CI 0.685-2.048). Pre-HCT MRD levels were significantly higher (P = 0.011) in participants transplanted within 120 days from diagnosis as well as in those treated with a FLT3 inhibitor pre-HCT and also transplanted within 120 days (P = 0.019). Pre-HCT MRD was dependent on both FLT3 inhibitor use and time to HCT, as participants treated with successive courses of chemotherapy + FLT3 inhibition had successively lower MRD by the time of HCT. Conclusions The time from AML diagnosis to HCT and FLT3 inhibitor use pre-HCT both appeared to impact MRD levels immediately prior to HCT, and geographic differences in these two practice patterns likely accounted for the regional differences in benefit from post-HCT gilteritinib observed in BMT CTN 1506. Successive courses of chemotherapy without FLT3 inhibition appears to have selected a more favorable risk (e.g., MRD-lower) population for enrollment. Successive courses of chemotherapy combined with FLT3 inhibition progressively eradicated MRD, such that a majority of participants undergoing HCT after 3 or 4 courses were MRD negative and therefore unlikely to benefit from post-HCT gilteritinib. These findings have implications for clinical practice. Increasing the number of courses of chemotherapy combined with FLT3 inhibition before HCT may lower MRD sufficiently to eliminate the need for post-HCT inhibition for some patients but, alternatively, the additional delay could increase the risk of pre-HCT relapse, preventing patients from receiving HCT in first remission.

T-cell engager therapies for the management of relapsed/refractory (R/R) multiple myeloma (MM) may lead to neutropenia with or without associated infections, which can limit treatment and efficacy. We present a case of a patient with penta-class R/R MM who, while receiving teclistamab, developed persistent severe to moderate neutropenia with associated infections. A review of her bone marrow confirmed the eradication of the malignant plasma cells, but flow cytometry identified an increase in T-cell large granular lymphocytes (T-LGLs). Upon further analysis, T-LGLs were found to be reactive and non-clonal, ruling out secondary T-LGL leukemia. This case describes the evolving peripheral blood cell counts, bone marrow composition, and radiologic findings due to the activation of the patient’s immune system before, during, and after treatment with teclistamab. To our knowledge, this is the first reported potential association of T-LGL activation with teclistamab treatment.

Abstract: We conducted a post hoc analysis of data from Blood and Marrow Transplant Clinical Trials Network 1506 (MORPHO), a randomized trial of gilteritinib vs placebo as posttransplantation maintenance for patients with FLT3-ITD–mutated acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT), focusing the interactions between conditioning regimen intensity, measurable residual disease (MRD), and NPM1 comutation status reported from diagnosis. Comparing FLT3-ITD MRD before and after conditioning, there was no difference between myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) in eradication or reduction of FLT3-ITD MRD. For participants who were FLT3-ITD MRD negative before HCT, there was no difference in the cumulative incidence of relapse during follow-up between those receiving MAC vs RIC. NPM1 comutation was associated with the largest magnitude of relapse-free survival benefit from post-HCT gilteritinib, and in these participants, post-HCT gilteritinib in the setting of RIC appeared to be as effective as MAC at preventing relapse. MAC appeared superior to RIC in preventing relapse only in participants who were NPM1 wild type at diagnosis and FLT3-ITD MRD positive before HCT. Our findings suggest that only a subset of patients with FLT3-ITD AML undergoing HCT may benefit from MAC and that, similar to AML therapy before HCT, the intensity of the HCT regimen should be adapted according to the molecular features of the disease. This trial was registered at www.clinicaltrials.gov as #NCT02997202.

A phase 1b study was conducted to evaluate the safety and feasibility of ciprofloxacin and etoposide combination treatment in subjects with relapsed and refractory acute myeloid leukemia. Eleven subjects were enrolled in the study. Utilizing the standard '3 + 3' design, escalating ciprofloxacin doses (750 mg, 1000 mg) twice daily on D1-D10 in combination with a fixed dose (200 mg) of etoposide on D2-D8 were administered. Maximum tolerated dose was determined to be 1000 mg of ciprofloxacin in combination with 200 mg of etoposide. Serious adverse events occurred in 54.5% (n = 6) subjects and 91% (n = 10) subjects reported ≥ grade 3 toxicities. Nine subjects completed treatment, one had a dose-limiting toxicity, and one withdrew. One subject achieved complete remission with a duration of 111 days and one subject achieved morphologic leukemia-free state after cycle 1. While the combination demonstrated safety and an acceptable toxicity profile, only modest hematologic and clinical benefits were observed.This trial was registered at www.clinicaltrials.gov as #NCT02773732.

Introduction: Multiple Myeloma (MM) is an incurable hematologic malignancy which requires close monitoring of disease status for appropriate ongoing management. The absence of detectable minimal/measurable residual disease (MRD) in the bone marrow has been shown to be highly predictive of survival in MM (Mazzotti et al. Blood Adv 2018); however, serial sampling of the bone marrow is not practical as a biomarker for MRD. While serum soluble B-cell maturation antigen (sBCMA) has been noted to correlate with disease activity and to be associated with response or progression of disease (Sanchez et al. Clin Cancer Res 2016; Ghermezi et al. Haematologica 2017), it has not been evaluated extensively as a marker of MRD. In this prospective observational correlative study, we assessed paired peripheral blood and bone marrow specimens in patients with MM post systemic therapy to determine the relationship between serum sBCMA and bone marrow MRD, as well as serum sBCMA and serum standard myeloma markers. Methods: Adult patients with MM who received standard of care systemic therapy, achieving at least a partial response per International Myeloma Working Group (IMWG) Uniform Response Criteria, and who eventually proceeded to first or salvage autologous hematopoietic stem cell transplantation with melphalan conditioning at our institution between 3/2023 and 6/2024 were included. Patients who received anti-BCMA therapy or investigational agents prior to transplant were excluded.Bonemarrow MRD was assessed by standard MRD flow cytometry with a limit of detection (LOD) of 10-3 and/or Next Generation Sequencing with a LOD of 10-6 (5 mL and 2 mL bone marrow aspirate samples, respectively). Serum sBCMA was measured by a sandwich enzyme-linked immunosorbent assay (1 mL whole blood samples). Serum standard myeloma markers included immunoglobulins (Ig), immunoglobulin free light chains, monoclonal spike (M-spike), and immunofixation (IFE). The relationship between sBCMA and clinical response status was determined by Pearson correlation. Comparisons between myeloma markers were made by applying the Welch Two Sample t-test. Results: Twenty-nine patients were included in the study. Their median age was 65 (range, 44-78) years and 22 were male. There were 22 white, 20 non-Hispanic/7 black, all non-Hispanic patients. Fourteen patients were diagnosed with IgG kappa, 2 with IgG lambda, 4 with IgA kappa, 4 with IgA lambda, 3 with kappa light chain (KLC), and 2 with lambda light chain (LLC) MM. Per Durie-Salmon Staging, 9 patients had stage IIA-IIIB MM; per Revised International Staging System, 10 patients had stage I-III MM; and stage was not available for 10 patients. Fourteen patients had received systemic therapy with a triplet regimen containing lenalidomide/bortezomib/dexamethasone, 9 patients a quadruplet regimen with daratumumab-lenalidomide/bortezomib/dexamethasone, 3 patients other triplet regimens, and 3 patients two lines of therapy for disease control; 5 patients had supplemental radiation therapy. Twelve patients had achieved partial response, 12 very good partial response, 3 complete response, and 2 stringent complete response. Post-systemic therapy, the mean (standard deviation) of serum sBCMA was 19.3 (12.2) ng/mL; KLC 2.9 (2.6) mg/dL, LLC 4.2 (4.7) mg/dL, KLC/LLC ratio 2.5 (2.4), IgG 674.6 (250.9) mg/dL, IgA 325.5 (189.4) mg/dL. Higher levels of sBCMA correlated with higher levels of tumor burden by IMWG response category (Pearson coefficient r= 0.4, p= 0.02). Bone marrow overt disease (< 15% malignant plasma cells) was present in 11 patients and MRD in 20 patients, with MRD not available for 2 patients. Nine patients had MRD only and 7 patients had no overt disease or detectable MRD. The mean value of sBCMA was significantly associated with the presence of bone marrow overt disease (p= 0.004) and with MRD only/no overt disease or detectable MRD (p= 0.04). In addition, the mean value of sBCMA was associated with elevated KLC (p< 0.001) and KLC/LLC ratio (p= 0.005), but not elevated LLC (p= 0.3), IgG (p= 0.7) or IgA (p= 0.9), or positive M-spike (p= 0.1) or IFE (p= 0.3). Conclusions: Serum sBCMA was associated not only with bone marrow overt disease and elevated serum KLC/LLC ratio, but also with bone marrow detectable or below LOD MRD. Further evaluation of sBCMA is warranted to evaluate it as a potential non-invasive biomarker of MRD in patients with MM.

Myelodysplastic neoplasms (MDS) define clonal hematopoietic malignancies characterized by heterogeneous mutational and clinical spectra typically seen in the elderly. Curative treatment entails allogeneic hematopoietic stem cell transplant, which is often not a feasible option due to older age and significant comorbidities. Immunotherapy has the cytotoxic capacity to elicit tumor-specific killing with long-term immunological memory. While a number of platforms have emerged, therapeutic vaccination presents as an appealing strategy for MDS given its promising safety profile and amenability for commercialization. Several preclinical and clinical trials have investigated the efficacy of vaccines in MDS; these include peptide vaccines targeting tumor antigens, whole cell-based vaccines and dendritic cell-based vaccines. These therapeutic vaccines have shown acceptable safety profiles, but consistent clinical responses remain elusive despite robust immunological reactions. Combining vaccines with immunotherapeutic agents holds promise and requires further investigation. Herein, we highlight therapeutic vaccine trials while reviewing challenges and future directions of successful vaccination strategies in MDS.

Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of

Post-transplant cyclophosphamide (PTCy) is increasingly used to reduce graft-versus-host disease after hematopoietic cell transplantation (HCT); however, it might be associated with more infections. All patients who were ≥2 years old, receiving haploidentical or matched sibling donor (Sib) HCT for acute leukemias or myelodysplastic syndrome, and either calcineurin inhibitor (CNI)- or PTCy-based GVHD prophylaxis [Haploidentical HCT with PTCy (HaploCy), 757; Sibling with PTCy (SibCy), 403; Sibling with CNI-based (SibCNI), 1605] were included. Most bacterial infections occurred within the first 100 days; 953 patients (34.5%) had at least 1 infection and 352 patients (13%) had ≥2 infections. Patients receiving PTCy had a greater incidence of bacterial infections by day 180 [HaploCy 46%; SibCy 48%; SibCNI 35%; p < 0.001]. Compared with the SibCNI without infection cohort, 1.99-fold, 3.33-fold, 2.78-fold, and 2.53-fold increased TRM was seen for the HaploCy cohort without infection and HaploCy, SibCy, and SibCNI cohorts with infection, respectively. Bacterial infections increased mortality [HaploCy (HR1.84, 99% CI: 1.45–2.33, p < 0.0001), SibCy cohort (HR,1.68, 99% CI: 1.30–2.19, p < 0.0001), and SibCNI cohort (HR,1.76, 99% CI: 1.43–2.16, p < 0.0001). PTCy was associated with increased bacterial infections regardless of donor, and bacterial infections were associated with increased mortality irrespective of GVHD prophylaxis. Patients receiving PTCy should be monitored carefully for bacterial infections following PTCy.

We aim to evaluate impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using CIBMTR registry data for HCTs done between 2013 and 2019. In all 1597 undergoing HCT for myelofibrosis, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study eligible, 1032 patients who received peripheral blood grafts for chronic phase myelofibrosis, 38% recipients of haploidentical-HCT were of non-White/Caucasian ethnicity. Matched sibling donor (MSD)-HCTs were independently associated with superior overall survival (OS) in the first 3 months [reference MSD, haploidentical HR 5.80 (95% CI 2.52-13.35), matched unrelated HR 4.50 (95% CI 2.24-9.03), and mismatched unrelated HR 5.13 (95% CI 1.44-18.31), P<0.001]. This difference in OS aligns with lower graft failure with MSD [haploidentical HR 6.11 (95%CI 2.98-12.54), matched unrelated HR 2.33 (95%CI 1.20-4.51), mismatched unrelated HR 1.82 (95%CI 0.58-5.72). There was no significant difference in OS among haploidentical, matched unrelated, and mismatched unrelated donor HCTs in the first 3 months. Donor type was not associated with differences in OS beyond 3 months post-HCT, relapse, disease-free survival or OS among patients who underwent HCT within 24 months of diagnosis. Patients who experienced graft failure had more advanced disease and commonly used nonmyeloablative conditioning. While MSDs remain a superior donor option due to improved engraftment, there is no significant difference in HCT outcomes from haploidentical and matched unrelated donors. These results establish haploidentical-HCT with posttransplantation cyclophosphamide as a viable option in myelofibrosis, especially for ethnic minorities underrepresented in the donor registries.

Stroke remains a leading cause of death and disability in the US, and time-limited reperfusion strategies remain the only approved treatment options. To address this unmet clinical need, we conducted a phase II randomized clinical trial to determine whether intravenous infusion of banked, non-HLA matched unrelated donor umbilical cord blood (UCB) improved functional outcome after stroke. Participants were randomized 2:1 to UCB or placebo within strata of National Institutes of Health Stroke Scale Score (NIHSS) and study center. Study product was infused 3-10 days following index stroke. The primary endpoint was change in modified Rankin Scale (mRS) from baseline to day 90. Key secondary outcomes included functional independence, NIHSS, the Barthel Index, and assessment of adverse events. The trial was terminated early due to slow accrual and logistical concerns associated with the COVID-19 pandemic, and a total of 73 of a planned 100 participants were included in primary analyses. The median (range) of the change in mRS was 1 point (-2, 3) in UCB and 1 point (-1,4) in Placebo (P = 0.72). A shift analysis comparing the mRS at day 90 utilizing proportional odds modeling showed a common odds ratio of 0.9 (95% CI: 0.4, 2.3) after adjustment for baseline NIHSS and randomization strata. The distribution of adverse events was similar between arms. Although this study did not suggest any safety concerns related to UCB in ischemic stroke, we did not show a clinical benefit in the reduced sample size evaluated.

PURPOSE Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 ( FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202 ) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. METHODS Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. RESULTS Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). CONCLUSION Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.

IntroductionTimely autologous hematopoietic stem cell transplantation (ASCT) is considered to be of the essence when used as consolidation therapy in large B-cell lymphoma (LBCL). It is common practice for patients awaiting ASCT to continue receiving chemotherapy to ensure disease control.ObjectivesThe purpose of this study is to evaluate this common practice, for which evidence is lacking, in relation to the timing of transplants.MethodsWe retrospectively reviewed the records of patients with LBCL who were considered for ASCT at our institution between 2011 and 2022. A transplant was described as “delayed” by the treating physician. Receipt of “additional” chemotherapy in patients pending ASCT was defined as the continuation of therapy past the number of minimum planned cycles ± radiologic confirmation of partial or complete response (PR/CR) at the treating physician's discretion. Patient groups were compared by Fisher's exact test.ResultsIncluded were 87 patients with LBCL who had achieved either PR or CR to their latest chemoimmunotherapy and were being evaluated for ASCT. Median age was 61 (range, 18-77) years and 55 (63%) were men. The majority, 62 (71%), of patients had advanced stage (III-IV) lymphoma with the most common entity identified as diffuse large B-cell lymphoma, not otherwise specified, diagnosed in 60 (69%) patients. ASCT was used for relapsed/refractory LBCL in 74 (85%) patients. Transplant was delayed in 20 (23%) patients (12 due to medical issues, 5 due to administrative issues, 3 due to both), 22 (25%) patients (6 delayed) received additional chemotherapy, and 14 (16%) patients (13 in CR, 1 in PR) had progression of disease (PD) while awaiting transplant. After their initial evaluation, 12 patients did not undergo transplant: 7 experienced PD requiring another line of therapy, 3 failed stem cell mobilization/collection, and 2 were ineligible due to high-risk comorbidities. For those who underwent a non-delayed transplant (n= 58), the median time between initial ASCT consult and ASCT was 79 (range, 30-305) days, while for those who underwent a delayed transplant (n= 17) 144 (range, 55-415) days. Delay of transplant was associated with significantly higher PD prior to transplant (OR= 4.61, P= 0.015) (Figure 1). Additional chemotherapy use did not predict significantly lower PD prior to transplant (OR= 1.83, P= 0.33) (Figure 2), including in patients whose transplant was delayed (OR= 0.9, P= 0.99).ConclusionTimely ASCT is associated with less progression of disease prior to transplant in patients with LBCL, while additional chemotherapy while awaiting ASCT is not. The role of chemotherapy continuation past PR/CR status in this group of patients needs to be studied prospectively.

Background: As the number of elderly patients referred to and undergoing allogeneic hematopoietic cell transplantation (alloHCT) continues to rise, there is a growing need for a comprehensive risk assessment model to accurately predict transplantation outcomes in this specific patient population. The widely used Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) does not fully capture factors influencing transplant outcomes in elderly patients. This study aims to enhance risk stratification for elderly patients undergoing alloHCT by integrating additional functional, nutritional, and clinical indicators. Methods: This is a retrospective study utilizing the data registry of HCT patients who received their treatment at UF Health Cancer Center. The inclusion criteria included all patients age > 65 years, who underwent their first alloHSCT between January 2012 and December 2022, regardless of graft type, conditioning regimen, donor type, or graft source. Patient data were extracted through chart review. The primary endpoint was 1-year Overall Survival (OS). Prognostic significance of each variable was assessed using Cox proportional hazard models. We subsequently used all variables to build a comprehensive prediction model to assess 1-year survival outcomes in elderly patients undergoing alloHCT. The predictive model's performance was measured by the Concordance-statistic (c-statistic). Results: A total of 69 patients satisfied the inclusion criteria and were included in the analysis. Median age was 69 years (range 66-81) and 65.2% were male. Unrelated donors were used in 66.6% of patients, while the remainder received grafts from related donors. Most patients received peripheral blood stem cell grafts (91%). Myeloid malignancies comprised the most common indication for alloHCT in this group of patients (89.8%). 59.4% had abnormal cytogenetics. 35 variables were considered in the analysis. In the univariate analysis, variables with impact on 1-year OS post-transplant included creatinine (HR 3.35, CI 1.62-6.91, p=0.001), blood urea nitrogen (HR 1.03, CI 1.01-1.06, p=0.007), estimated glomerular filtration rate (HR 0.93, CI 0.89-0.93, p=0.001), hemoglobin (HR 0.8, CI 0.66-0.97, p=0.02), abnormal cytogenetics (HR 2.27, CI 1.20-4.31, p=0.012) and high and very high disease risk index (HR 0.51, CI 0.27-0.98, p=0.04). Notably, both hemoglobin and cytogenetics demonstrated a c-statistic greater than 0.6 in the univariate analysis. In the multivariate analysis, variables impacting 1-year OS included hemoglobin (HR 0.69, CI 0.48-0.99, p=0.04), remission status at the time of transplant i.e., not reached (NR) vs complete remission 1 (CR1) (HR 0.05, CI 0.00-0.71, p=0.027), and abnormal cytogenetics (HR 7.55, CI 2.32-24.58, p=0.001). Interestingly, the HCT-CI did not significantly impact 1-year OS in the univariate analysis (c-statistic 0.51, HR 0.99, CI 0.85-1.15, p=0.896). Our prediction model showed good performance with a mean area under the receiver operating characteristic curve of 0.82. Conclusion: We developed a comprehensive prediction model to assess 1-year OS in elderly patients undergoing alloHCT to overcome some of the limitations of the HCT-CI in this unique age group. This model holds potential to enhance decision-making regarding candidacy for elderly patients undergoing alloHCT.

e18663 Background: Despite the high survival associated with Hodgkin lymphoma (HL), established disparities exist both in survival for Black and Hispanic patients and their access to consolidative treatments like radiotherapy as demonstrated using large, population-based databases. Elderly patients with HL face inferior survival compared to younger patients. Brentuximab is an approved second line therapy for those patients with refractory/relapsed HL. We examined whether there were inequities in receipt of treatment among those diagnosed with HL in a contemporary cohort receiving frontline doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), allowing for evaluation of targeted therapy. Methods: Data from Surveillance Epidemiology and End-Results (SEER) linked to Medicare claims were used to identify individuals diagnosed with HL from 2008 to 2017 who received frontline treatment with ABVD using applicable Healthcare Common Procedure Coding System codes. We examined differences in associations with receipt of brentuximab following ABVD within two years of diagnosis. Descriptive statistics were used to characterize the sample. We ran univariable and multivariable logistic regression models (producing adjusted odds ratios, aOR and 95% confidence intervals, CI) predicting treatment with brentuximab. Multivariable models were adjusted for age at diagnosis, sex, race/ethnicity, stage, insurance at diagnosis, and geographic location. Results: A total of 2,651 people diagnosed with HL were identified, 2,007 (76%) of which survived two years and 1,475 (56%) were still alive at last follow-up in 2019. Mean age at diagnosis was 69 years (SD: 12.4), most were men (N = 1,457, 55%), non-Hispanic White (N = 2,050, 77%), Hispanic (N = 291, 11%), or non-Hispanic Black (N = 220, 8%), diagnosed with stage I or II disease (N = 1,591, 60%), and received radiotherapy (N = 663, 23%) or brentuximab (N = 181, 7%) within two years of diagnosis. On univariable analysis, race and ethnicity did not have a statistically significant association with receipt of brentuximab as adjuvant treatment within two years of diagnosis. On multivariable analysis, individuals without insurance at diagnosis (aOR 1.54; 95% CI 1.02, 2.30) or those diagnosed with stage III or IV disease (aOR 2.04; 95% CI 1.04, 2.98) were more likely to receive brentuximab as adjuvant treatment within two years of diagnosis, after adjusting for the variables described above. Conclusions: Although we cannot definitively say that receipt of brentuximab within two years of diagnosis following ABVD is due to relapse, we posit that this can be used as a proxy for relapse. Our analysis did not demonstrate that race and ethnicity rose to traditional levels of statistical significance regarding associations with decreased odds of receiving brentuximab. In multivariable analysis, patients without insurance or diagnosed with stage III or IV disease were more likely to receive brentuximab.

Background: Acute erythroid leukemia (AEL), also known as pure erythroid leukemia, is a rare subtype of acute myeloid leukemia (AML) characterized by the proliferation of malignant erythroid precursors. Outcome data at the population level are scarce. Methods: We performed a retrospective analysis of the Surveillance Epidemiology and End Results (SEER) database. All cases with a histologically confirmed diagnosis of acute (pure) erythroid leukemia during the period of 2000–2019 were included in the study. The Kaplan–Meier method was used to perform survival analysis. The significance of differences between overall survival (OS) was analyzed using the log-rank test. Results: In total, 968 patients were included in the study. The median age was 68 years (range 0–95), 62% of patients were males, and 62.5% (n = 605) were treated with chemotherapy. The median OS for <18, 18–49, 50–64, 65–79 and 80+ age groups was 69, 18, 8, 3 and 1 month, respectively (p < 0.0001). Patients who received chemotherapy had significantly improved OS compared to patients who did not, among both adults (p < 0.0001) and children (p = 0.004). There were no significant differences in OS based on sex, race, ethnicity and median household income. Median OS for adults diagnosed in 2000–2004, 2005–2009, 2010–2014, 2015–2019 was 4, 6, 6 and 3 months, respectively, with no significant differences in OS between these groups. Conclusion: AEL occurs in all age groups but is most common in the elderly. Outcomes are poor with current chemotherapeutic agents, with no improvement in the last two decades. This study stresses the urgent need for investigational agents.